| Autor: |
Niayesh Razi, Weizhong Li, Maxinne A. Ignacio, Jeffrey M. Loube, Eva L. Agostino, Xiaoping Zhu, Margaret A. Scull, Jeffrey J. DeStefano |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Respiratory Research, Vol 24, Iss 1, Pp 1-11 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1465-993X |
| DOI: |
10.1186/s12931-023-02590-4 |
| Popis: |
Abstract Background SARS-CoV-2, the agent responsible for the COVID-19 pandemic, enters cells through viral spike glycoprotein binding to the cellular receptor, angiotensin-converting enzyme 2 (ACE2). Given the lack of effective antivirals targeting SARS-CoV-2, we previously utilized systematic evolution of ligands by exponential enrichment (SELEX) and selected fluoro-arabino nucleic acid (FANA) aptamer R8-9 that was able to block the interaction between the viral receptor-binding domain and ACE2. Methods Here, we further assessed FANA-R8-9 as an entry inhibitor in contexts that recapitulate infection in vivo. Results We demonstrate that FANA-R8-9 inhibits spike-bearing pseudovirus particle uptake in cell lines. Then, using an in-vitro model of human airway epithelium (HAE) and SARS-CoV-2 virus, we show that FANA-R8-9 significantly reduces viral infection when added either at the time of inoculation, or several hours later. These results were specific to the R8-9 sequence, not the xeno-nucleic acid utilized to make the aptamer. Importantly, we also show that FANA-R8-9 is stable in HAE culture secretions and has no overt cytotoxic effects. Conclusions Together, these results suggest that FANA-R8-9 effectively prevents infection by specific SARS-CoV-2 variants and indicate that aptamer technology could be utilized to target other clinically-relevant viruses in the respiratory mucosa. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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